This invention relates to a method and apparatus for forming ions from an analyte, more particularly for forming ions from an analyte dissolved in a liquid. Usually, the generated ions are directed into a mass analyzer, typically a mass spectrometer. The present invention also relates to an ion source probe use in such a method or apparatus.
There are presently available a wide variety of mass spectrometer and mass analyzer systems. A common and necessary requirement for any mass spectrometer is to first ionize an analyte of interest, prior to introduction into the mass spectrometer. For this purpose, numerous different ionization techniques have been developed. Many analytes, particularly larger or organic compounds, must be ionized with care, to ensure that the analyte is not degraded by the ionization process. A commonly used ion source is an electrospray interface, which is used to receive a liquid sample containing a dissolved analyte, typically from a source such as a liquid chromatograph (xe2x80x9cLCxe2x80x9d). Liquid from the LC is directed through a free end of a capillary tube connected to one pole of a high voltage source, and the tube is mounted opposite and spaced from an orifice plate connected to the other pole of the high voltage source. An orifice in the orifice plate leads, directly or indirectly, into the mass analyzer vacuum chamber. This results in the electric field between the capillary tube and the orifice plate generating a spray of charged droplets producing a liquid flow without a pump, and the droplets evaporate to leave analyte ions to pass through the orifice into the mass analyzer vacuum chamber.
Electrospray has a limitation that it can only handle relatively small flows, since larger flows produce larger droplets, causing the ion signal to fall off and become unstable. Typically, electrospray can handle flows up to about 10 microlitres per minute. Consequently, this technique was refined into a technique known as a nebulizer gas spray technique, as disclosed, for example, in U.S. Pat. No. 4,861,988 to Cornell Research Foundation. In the nebulizer technique, an additional co-current of high velocity nebulizer gas is provided co-axial with the capillary tube. The nebulizer gas nebulizes the liquid to produce a mist of droplets which are charged by the applied electric field. The gas serves to break up the droplets and promote vaporization of the solvent, enabling higher flow rates to be used. Nebulizer gas spray functions reasonably well and liquid flows of up to between 100 and 200 microlitres per minute. However, even with the nebulizer gas spray, it has been found that with liquid flows of the order of about 100 microlitres per minute, the sensitivity of the instrument is less than at lower flows, and that the sensitivity reduces substantially for liquid flows above about 100 microlitres per minute. It is believed that at least part of the problem is that at higher liquid flows, larger droplets are produced and do not evaporate before these droplets reach the orifice plate. Therefore, much sample is lost.
Another attempt to improve on the nebulizer technique is disclosed in U.S. Pat. No. 5,412,208 to Thomas R. Covey, one of the inventors of the present invention, and Jospeh F. Anacleto, (and assigned to this same assignee of the present invention). This patent discloses an ion spray technique that is now marketed under the trademark TURBOION SPRAY, and has enjoyed some considerable success. The basic principle behind this technique, which was developed as an improvement on the earlier nebulizer technique, is to provide a flow of heated gas in a second direction, at an angle to the direction of the basic nebulizer tube, so that the flow of heated gas intersects with the spray generated from the tip of a nebulizer tube. This intersection region is located upstream of the orifice, causing the flows to mix turbulently, whereby the second flow promotes evaporation of the droplets. It is also believed that the second flow helps move droplets towards the orifice, providing a focusing effect and providing better sensitivity. It is also mentioned in this patent that the flows could be provided opposing one another and perpendicular to the axis through the orifice. The intention is that the natural gas flow from the atmospheric flow pressure ionization region into the vacuum chamber of the mass analyzer would draw droplets towards the orifice and hence promote movement of ions into the mass analyzer.
This U.S. Pat. No. 5,412,208 also proposes the use of a second heated gas flow or jet. The only specific configuration mentioned is to provide a first gas flow opposed to the nebulizer, with both this gas flow and the nebulizer perpendicular to the orifice, and then provide a second gas flow aligned with the axis of the orifice, so as to be perpendicular to the nebulizer and the first gas chamber. However, this arrangement is not discussed in any great detail, and indeed the patent specifically teaches that it is preferred to use just one gas flow, so as to avoid the complication of balancing three gas flows (the two separate gas flows and the gas flow required for the nebulizer). It also teaches that by suitably angling the tubes with just one gas jet, a net velocity component towards the orifice can be provided, without the requirement of a second, separate heated gas flow.
Further research by the inventors of the present application has revealed many short comings with this arrangement. Firstly, heaters previously used to heat the gas flow have proved inadequate and did not provide good heat exchange efficiency. Consequently, the gas is not heated to an optimum temperature. This deficiency was compounded by the manner in which the feed-back sensor was implemented; the set temperature is far higher than the gas temperature, as the set temperature is a measure of the heater temperature and not the gas temperature. The previous arrangements described in U.S. Pat. No. 5,412,208 provided a gas flow on just one side of the spray cone emitted from the nebulizer, which resulted in asymmetric heating and heat starvation. Typically, the axis of the nebulizer was directed to one side of the orifice, and the heated gas was then directed to the nebulizer spray on a side away from the orifice. This meant that heat did not penetrate sufficiently to the region of the spray adjacent the sampling orifice, so that droplets in the best position for generating ions for passage through the orifice were not adequately heated and desolvated. Hence, it was difficult to achieve maximum desolvation, especially at high flow rates. As the spray was sampled on the side opposite from the gas jet, a substantial amount of surrounding air is drawn in to the spray; in other words, rather ensuring that gas sampled through the orifice is a clean gas with a known composition, with this arrangement there is a tendency for ambient air to mix in with the spray. This draining in and mixing in of surrounding air or gas is entrainment, and this can contribute to high background levels. In order to provide good sensitivity, the spray was directed, if not directly at the orifice, to a location adjacent the orifice. This results in a high probability for larger drops to penetrate the curtain gas provided on the other side of the orifice, and these can then contribute to background noise levels.
In conventional ion sources, e.g. as in U.S. Pat. No. 5,412,208, large volumes of gas are drawn into the ionization region by the entrainment effect. Commonly, the composition of this external gas is uncontrolled, so that the gas is contaminated with chemical entities constituting chemical noise. Common and ubiquitous materials such as phthalates (plastics components) are present at high levels in all sources of gasses except those of a highly purified nature such as the entrainment gas of the present invention. While U.S. Pat. No. 5,412,208 does inject clean gas, it is ineffective, because it is asymmetrically injecting the gas on the wrong side., i.e. away from the orifice.
An important factor that is not even recognized in the earlier ""208 patent is that of the effect on performance on entrainment and recirculation. An expanding spray cone tends always to entrain surrounding gas, causing the cross-section of the spray cone to progressively increase and the mass flow rate to progressively increase; simultaneously, as surrounding gas is entrained, the average velocity of the spray cone tends to decrease. In an ionization chamber, this means that the gas in the chamber is entrained with the spray cone. As the spray is discharged within the chamber, remnants from the spray build-up within the gas, and are then recirculated back into the spray cone. This has a number of serious disadvantages. On the one hand, it gives a memory effect where, if the analyte in the spray is switched, the remaining spray in the ionization chamber containing a previous analyte still recirculates the prior analyte for some time. The result is that, in the ions stream entering the mass spectrometer, one does not observe a clean, abrupt switch from one analyte to the other, but rather the level of the previous analyte tends to trail off somewhat. Also, it can lead to build-up of solvents and other unwanted material within the spray chamber, increasing background chemical noise level.
In accordance with a first aspect of the present invention, there is provided a method of forming ions for analysis from a liquid sample comprising an analyte in a solvent liquid, the method comprising the steps of:
a) providing a capillary tube having a free end, and an orifice member spaced from the free-end of the capillary tube and having an orifice therein;
b) directing the liquid through the capillary tube and out the free-end, to form a first flow comprising a spray of droplets of the liquid sample, to promote vaporization of the solvent liquid;
c) generating an electric field between the free-end of the capillary and the orifice member, and thereby causing the droplets to be charged, and directing the first flow in a first direction along the axis of the capillary tube;
d) providing second and third flows, of a gas, and heating the second and third flows;
e) directing the second and third flows to intersect with the first flow at a selected mixing region, to promote turbulent mixing of the first, second and third flows, the first, second and third directions being different from one another, and each of the second and third directions being selected to provide each of the second and third flows with a velocity component in the first direction and a velocity component towards the axis of the capillary tube, thereby to promote entrainment of the heated gas in the spray, with the heated gas acting to assist the evaporation of the droplets to release ions there from;
drawing at least some of the ions produced from the droplets through the orifice for analysis.
In accordance with a second aspect of the present invention, there is provided a method of forming ions for analysis from a liquid sample comprising an analyte in a solvent liquid, the method comprising the steps of:
a) providing a capillary tube having a free end, and an orifice member spaced from the free-end of the capillary tube and having an orifice therein;
b) directing the liquid through the capillary tube and out the free-end, to form a first flow comprising a spray of droplets of the liquid sample, to promote vaporization of the solvent liquid;
c) generating an electric field between the free-end of the capillary and the orifice member, and thereby causing the droplets to be charged, and directing the first flow in a first direction along the axis of the capillary tube;
d) providing a continuous arc jet, of a gas, extending in an arc at least partially around the axis of the capillary tube and heating the arc jet of gas;
e) directing the arc jet of gas to intersect with the first flow at a selected mixing region, to promote turbulent mixing of the first flow and the arc jet of gas, all of the arc jet of gas being directed at an angle to the first direction, said angle being selected to provide all of the arc jet of gas with a velocity component in the first direction and a velocity component towards the axis of the capillary tube, thereby to promote entrainment of the heated gas in the spray, with the heated gas acting to assist the evaporation of the droplets to release ions therefrom;
f) drawing at least some of the ions produced from the droplets through the orifice for analysis.
It is to be noted that the arc jet of gas can be part of a circle, a semi-circle, or even a complete circle and it can be provided by a number of discrete jets or by one continuous jet. It is preferred that the outlets forming the gas jets be space radially outwardly away from the nebuliser or other outlet for the sample.
In accordance with a third aspect of the present invention, there is provided an apparatus for generating ions for analysis from a sample liquid containing an analyte, the apparatus comprising:
a) an ion source housing defining an ion source chamber;
b) a capillary tube, for receiving the liquid and having a first free end in the chamber for discharging the liquid into the chamber as a first flow comprising a spray of droplets;
c) an orifice member in the housing and having an orifice therein providing communications between the ion source chamber and the exterior thereof, the orifice being spaced from the free end of the capillary tube;
d) connections for the capillary tube and the orifice member, for connection to a power source, to generate an electric field between the free end of the capillary tube and the orifice member; and
e) two gas sources, each gas source comprising a heater for the gas and a gas outlet, for generating second and third flows, of gas, wherein the second and third flows are directed to intersect with the first flow at a selected mixing region for turbulent mixing of the first, second and third flows, the first, second and third directions being different from one another, and each of the second and third directions providing the second and third flows with a velocity component in the first direction and a velocity component towards the axis of the capillary tube, whereby in use, the spray formed from the first flow turbulently mixes with heated gas of the second and third flows in the selected region, to promote evaporation of droplets of the liquid in the first flow to release ions therefrom and whereby the ions pass through the orifice for analysis.
In accordance with a fourth aspect of the present invention, there is provided an apparatus for generating ions for analysis from a sample liquid containing an analyte, the apparatus comprising:
a) an ion source housing defining an ion source chamber;
b) a capillary tube, for receiving the liquid and having a first free end in the chamber for discharging the liquid into the chamber as a first flow comprising a spray of droplets;
c) an orifice member in the housing and having an orifice therein providing communications between the ion source chamber and the exterior thereof, the orifice being spaced from the free end of the capillary tube;
d) connections for the capillary tube and the orifice member, for connection to a power source, to generate an electric field between the free end of the capillary tube and the orifice member;
e) a gas source, comprising a heater for the gas and an arc-shaped gas outlet, for generating an arc jet, of gas, wherein the arc jet is directed at an angle to the first direction, to intersect with the first flow at a selected mixing region for turbulent mixing of the first flow and the arc jet of gas, the angle being such as to provide all of the gas of said arc jet with a velocity component in the first direction and a velocity component towards the axis of the capillary tube, whereby in use, the spray formed from the first flow turbulently mixes with heated gas of the arc jet in the selected region, to promote evaporation of droplets of the liquid in the first flow to release ions therefrom and whereby the ions pass through the orifice for analysis.
Again, the gas outlet can be a single jet or a plurality of discrete jets, and the arc shape can encompass any angle from less than a semi-circle to a full circle.
In accordance with a fifth aspect of the present invention, there is provided an apparatus for generating ions from a liquid sample comprising a solvent liquid and an analyte dissolved therein, the apparatus comprising:
a) an ion source housing defining an ion source chamber;
b) at least one ion source within the ion source housing for generating a spray of droplets of the liquid sample;
c) an orifice member in the ion source housing having an orifice therein and being spaced from the ion source;
d) connections for connecting the orifice member and the ion source to a power supply for generating an electric field therebetween;
e) at least one gas source having a heater and a gas outlet, each gas source being mounted in the ion source housing and being directed in a direction towards a selection mixing region, to promote turbulent mixing of the spray and the gas;
f) a primary exhaust outlet in the ion source housing located adjacent and downstream from the selected region, to reduce recirculation of spent gas and liquid sample within the ion source housing.
The primary exhaust outlet can be provided by a tube extending into the housing and/or by a modification to the housing bringing the bottom (assuming that as is conventional the ion source is mounted in the top facing downwards) of the housing closed to the orifice for ions.
In accordance with a sixth aspect of the present invention, there is provided an atmospheric pressure chemical ionization source comprising:
a) a tubular ceramic body defining a substantially tubular flash desorption chamber, opened at one end and closed at the other end;
b) a supply tube extending through the closed end of the body to provide at least a spray of a liquid sample containing an analyte dissolved in a solvent liquid; and
c) an electrical resistive heating element formed within the ceramic for heating the ceramic to a temperature sufficient to cause flash vaporization of droplets of the liquid sample.
This heater configuration is well suited for implementing another aspect of the present invention, although generally this can be implemented with any suitable heater. This provides, preferably as part of an ion source housing, a heater, preferably tubular, configured to accept either a nebuliser probe or an APCI probe. A probe for a corona discharge is preferably movably mounted adjacent an outlet of the heater. For a nebuliser probe, the heater acts just as a holder and the outlet of the nebuliser probe would be located close to the outlet of the heater. For the APCI probe, the actual probe would have its outlet located within the heater so that the spray therefrom is heated etc. by the heater, which is then actuated. The APCI probe preferably has no auxiliary gas flow so as to have an outside diameter that can generally correspond to that for the nebuliser probe.
Finally, corresponding to the sixth aspect above, a seventh aspect of the present invention provides a method of forming ions by atmospheric chemical pressure ionization, the method comprising:
a) providing a capillary tube with a free end for forming a spray from a liquid sample comprising a solvent liquid and an analyte dissolved therein;
b) providing a flow of a gas to promote evaporation of the solvent liquid;
c) providing a heated surface around the spray and heating the surface to a temperature sufficient to promote flash vaporization of liquid droplets and prevent substantial contamination of the heater surface by the Leidenfrost effect;
d) providing a corona discharge to ionize free analyte molecules.